"Antibodies that target CTLA-4 can stimulate anti-cancer immunity but also cause off-target inflammatory pathologies in the gut. We established a new mouse model of colitis that is triggered by CTLA-4 blockade, and determined that this inflammatory side effect is caused by the Fc domain of the anti-CTLA-4 antibodies which leads to the depletion of a subset of immune suppressive regulatory T cells in the gut. Notably, we found that anti-CTLA-4 nanobodies which lack an Fc domain can effectively promote anti-cancer responses without causing colitis."
Pictured left to right: Dr. Bernard Lo, Ph.D. (Research Investigator, Pathology, University of Michigan) and Dr. Gabriel Núñez, M.D. (Professor, Pathology, University of Michigan)